Clinical and Metabolic Characterization of Adults With Type 2 Diabetes by Age in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) Cohort
Authors: Vanita R. Aroda, Heidi Krause-Steinrauf, Erin J. Kazemi, John B. Buse, Barbara I. Gulanski, Hermes J. Florez, Andrew J. Ahmann, Amy Loveland, Alexander Kuhn, Jacqueline Y. Lonier, Deborah J. Wexler, J.P. Crandall, M.D. McKee, S. Behringer-Massera, J. Brown-Friday, E. Xhori, K. Ballentine-Cargill, S. Duran, H. Estrella, S. Gonzalez de la torre, J. Lukin, L.S. Phillips, E. Burgess, D. Olson, M. Rhee, P. Wilson, T.S. Raines, J. Boers, J. Costello, M. Maher-Albertelli, R. Mungara, L. Savoye, C.A. White, C. Gullett, L. Holloway, F. Morehead, S. Person, M. Sibymon, S. Tanukonda, C. Adams, A. Ross, A. Balasubramanyam, R. Gaba, E. Gonzalez Hattery, A. Ideozu, J. Jimenez, G. Montes, C. Wright, P. Hollander, E. Roe, A. Jackson, A. Smiley, P. Burt, L. Estrada, K. Chionh, F. Ismail-Beigi, C. Falck-Ytter, L. Sayyed Kassem, A. Sood, M. Tiktin, T. Kulow, C. Newman, K.A. Stancil, B. Cramer, J. Iacoboni, M.V. Kononets, C. Sanders, L. Tucker, A. Werner, A. Maxwell, G. McPhee, C. Patel, L. Colosimo, A. Krol, R. Goland, J. Pring, L. Alfano, P. Kringas, C. Hausheer, J. Tejada, K. Gumpel, A. Kirpitch, H. Schneier, J.B. Green, H. AbouAssi, R. Chatterjee, M.N. Feinglos, J. English Jones, S.A. Khan, J.B. Kimpel, R.P. Zimmer, M. Furst, B.M. Satterwhite, C.R. Thacker, K. Evans Kreider, C.N. Mariash, K.J. Mather, H.M. Ismail, A. Lteif, M. Mullen, T. Hamilton, N. Patel, G. Riera, M. Jackson, V. Pirics, D. Aguillar, D. Howard, S. Hurt, R. Bergenstal, A. Carlson, T. Martens, M. Johnson, R. Hill, J. Hyatt, C. Jensen, M. Madden, D. Martin, H. Willis, W. Konerza, S. Yang, K. Kleeberger, R. Passi, S. Fortmann, M. Herson, K. Mularski, H. Glauber, J. Prihoda, B. Ash, C. Carlson, P.A. Ramey, E. Schield, B. Torgrimson-Ojerio, K. Arnold, B. Kauffman, E. Panos, S. Sahnow, K. Bays, K. Berame, J. Cook, D. Ghioni, J. Gluth, K. Schell, J. Criscola, C. Friason, S. Jones, S. Nazarov, J. Barzilay, N. Rassouli, R. Puttnam, B. Ojoawo, R. Nelson, M. Curtis, B. Hollis, C. Sanders-Jones, K. Stokes, Z. El-Haqq, A. Kolli, T. Tran, D. Wexler, M. Larkin, J. Meigs, B. Chambers, A. Dushkin, G. Rocchio, M. Yepes, B. Steiner, H. Dulin, M. Cayford, K. Chu, A. DeManbey, M. Hillard, K. Martin, N. Thangthaeng, L. Gurry, R. Kochis, E. Raymond, V. Ripley, C. Stevens, J. Park, V. Aroda, A. Ghazi, M. Magee, Ann Ressing, A. Loveland, M. Hamm, M. Hurtado, A. Kuhn, J. Leger, L. Manandhar, O. Sanchez, T. Young, F. Mofor, R. Garg, V. Lagari-Libhaber, H.J. Florez, W.M. Valencia, J. Marks, S. Casula, L. Oropesa-Gonzalez, L. Hue, A. Cuadot, R. Nieto-Martinez, A.K. Riccio Veliz, M. Gutt, Y.J. Kendal, B. Veciana, A. Ahmann, D. Aby-Daniel, F. Joarder, V. Morimoto, C. Sprague, D. Yamashita, N. Cady, N. Rivera-Eschright, P. Kirchhoff, B. Morales Gomez, J. Adducci, A. Goncharova, S.H. Hox, H. Petrovitch, M. Matwichyna, V. Jenkins, L. Broadwater, R.R. Ishii, N.O. Bermudez, D.S. Hsia, W.T. Cefalu, F.L. Greenway, C. Waguespack, E. King, G. Fry, A. Dragg, B. Gildersleeve, J. Arceneaux, N. Haynes, A. Thomassie, M. Pavlionis, B. Bourgeois, C. Hazlett, S. Mudaliar, R. Henry, S. Boeder, J. Pettus, E. Diaz, D. Garcia-Acosta, S. Maggs, C. DeLue, A. Stallings, E. Castro, S. Hernandez, J. Krakoff, J.M. Curtis, T. Killean, M. Khalid, E. Joshevama, E. Diaz, D. Martin, K. Tsingine, T. Karshner, J. Albu, F.X. Pi-Sunyer, S. Frances, C. Maggio, E. Ellis, J. Bastawrose, X. Gong, M.A. Banerji, P. August, M. Lee, D. Lorber, N.M. Brown, D.H. Josephson, L.L. Thomas, M. Tsovian, A. Cherian, M.H. Jacobson, M.M. Mishko, M.S. Kirkman, J.B. Buse, J. Dostou, S. Machineni, L. Young, K. Bergamo, A. Goley, J. Kerr, J.F. Largay, S. Guarda, J. Cuffee, D. Culmer, R. Fraser, H. Almeida, S. Coffer, E. Debnam, L. Kiker, S. Morton, K. Josey, G. Fuller, W.T. Garvey, A.L. Cherrington, D. Dyer, M.C.R. Lawson, O. Griffith, A. Agne, S. McCullars, R.M. Cohen, J. Craig, M.C. Rogge, K. Burton, K. Kersey, C. Wilson, S. Lipp, M.B. Vonder Meulen, C. Adkins, T. Onadeko, N. Rasouli, C. Baker, E. Schroeder, M. Razzaghi, C. Lyon, R. Penaloza, C. Underkofler, R. Lorch, S. Douglass, S. Steiner, W.I. Sivitz, E. Cline, L.K. Knosp, J. McConnell, T. Lowe, W.H. Herman, R. Pop-Busui, M.H. Tan, C. Martin, A. Waltje, A. Katona, L. Goodhall, R. Eggleston, S. Kuo, S. Bojescu, S. Bule, N. Kessler, E. LaSalle, K. Whitley, E.R. Seaquist, A. Bantle, T. Harindhanavudhi, A. Kumar, B. Redmon, J. Bantle, M. Coe, M. Mech, A. Taddese, L. Lesne, S. Smith, C. Desouza, L. Kuechenmeister, V. Shivaswamy, S. Burbach, M.G. Rodriguez, K. Seipel, A. Alfred, A.L. Morales, J. Eggert, G. Lord, W. Taylor, R. Tillson, D.S. Schade, A. Adolphe, M. Burge, E. Duran-Valdez, J. Martinez, A. Bancroft, S. Kunkel, F. Ali Jamaleddin Ahmad, D. Hernandez McGinnis, B. Pucchetti, E. Scripsick, A. Zamorano, R.A. DeFronzo, E. Cersosimo, M. Abdul-Ghani, C. Triplitt, D. Juarez, M. Mullen, R.I. Garza, H. Verastiqui, K. Wright, C. Puckett, P. Raskin, C. Rhee, S. Abraham, L.F. Jordan, S. Sao, L. Morton, O. Smith, L. Osornio Walker, L. Schnurr-Breen, R. Ayala, R.B. Kreymer, D. Sturgess, K.M. Utzschneider, S.E. Kahn, L. Alarcon-Casas, L. Wright, E.J. Boyko, E.C. Tsai, D.L. Trence, S. Trikudanathan, B.N. Fattaleh, B.K. Montgomery, K.M. Atkinson, A. Kozedub, T. Concepcion, C. Moak, N. Prikhodko, S. Rhothisen, T.A. Elasy, S. Martin, L. Shackelford, R. Goidel, N. Hinkle, C. Lovell, J. Myers, J. Lipps Hogan, J.B. McGill, M. Salam, T. Schweiger, S. Kissel, C. Recklein, M.J. Clifton, W. Tamborlane, A. Camp, B. Gulanski, S.E. Inzucchi, K. Pham, M. Alguard, P. Gatcomb, K. Lessard, M. Perez, L. Iannone, E. Magenheimer, A. Montosa, H.B. Burch, A.A. Bremer, J. Fradkin, D.M. Nathan, J.M. Lachin, H. Krause-Steinrauf, N. Younes, M. Backman, I. Bebu, N. Butera, C.J. Buys, A. Fagan Murphy, Y. Gao, A. Ghosh, M.R. Gramzinski, E. Kazemi, S.D. Hall, E. Legowski, C. Suratt, M. Tripputi, A. Arey, J. Bethepu, C. Lund, P. Mangat Dhaliwal, P. McGee, E. Mesimer, L. Ngo, M. Steffes, J. Seegmiller, A. Saenger, V. Arends, D. Gabrielson, T. Conner, S. Warren, J. Day, J. Huminik, A. Scrymgeour, E.Z. Soliman, Y. Pokharel, Z.M. Zhang, C. Campbell, J. Hu, L. Keasler, S. Hensley, Y. Li, W.H. Herman, S. Kuo, C. Martin, A. Waltje, R. Mihalcea, D.J. Min, V. Perez-Rosas, L. Prosser, K. Resnicow, W. Ye, H. Shao, P. Zhang, J. Luchsinger, D. Sanchez, S. Assuras, E. Groessl, F. Sakha, H. Chong, N. Hillery, B.M. Everett, I. Abdouch, G. Bahtiyar, P. Brantley, F.E. Broyles, G. Canaris, P. Copeland, J.J. Craine, W.L. Fein, A. Gliwa, L. Hope, M.S. Lee, R. Meiners, V. Meiners, H. O’Neal, J.E. Park, A. Sacerdote, E. Sledge, L. Soni, J. Steppel-Reznik, A. Turchin, B. Brooks-Worrell, C.S. Hampe, C.B. Newgard, J.P. Palmer, A. Shojaie, J. Higgins, L. Fischer, S. Golden, J. Gonzalez, A. Naik, E. Walker, L. Doner Lotenberg, J.M. Gallivan, J. Lim, D.M. Tuncer, S. Behringer-Massera
Journal: Diabetes Care (2022)

Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We sought to characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to treatment intensification. In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), participants were enrolled who had type 2 diabetes duration <10 years, had HbA1c 6.8-8.5%, and were on metformin monotherapy. Participants were randomly assigned to one of four additional glucose-lowering medications. We compared baseline clinical and metabolic characteristics across age categories (<45, 45 to <55, 55 to <65, and ≥65 years) using ANOVA and Pearson χ2 tests. Within the GRADE cohort (n = 5,047), we observed significant differences by age, with younger adults having greater racial diversity, fewer medications for common comorbidities, lower prevalence of CVD, higher weight and BMI, and more pronounced hyperglycemia and diabetic dyslipidemia and with metabolic profile indicating lower insulin sensitivity (inverse fasting insulin [1/(fasting insulin)], HOMA of steady-state insulin sensitivity, Matsuda index) and inadequate β-cell response (oral disposition index) (P < 0.05 across age categories). Clinical and metabolic characteristics of type 2 diabetes differ by age within the GRADE cohort. Younger adults exhibit more prominent obesity-related characteristics, including higher obesity levels and lower insulin sensitivity and β-cell compensation. Given the increasing burden of type 2 diabetes and complications, particularly among younger populations, these age-related distinctions may inform risk factor management approaches and treatment priorities. Further study will determine whether age-related differences impact response to therapy.